What progress has been made in fertility preservation (FP) over the last decade? FP techniques have been widely adopted over the last decade and therefore the establishment of international registries on their short- and long-term outcomes is strongly recommended. FP is a fundamental issue for both males and females whose future fertility may be compromised. Reproductive capacity may be seriously affected by age, different medical conditions and also by treatments, especially those with gonadal toxicity. There is general consensus on the need to provide counselling about currently available FP options to all individuals wishing to preserve their fertility. An international meeting with representatives from expert scientific societies involved in FP was held in Barcelona, Spain, in June 2015. Twenty international FP experts belonging to the American Society of Reproductive Medicine, ESHRE and the International Society of Fertility Preservation reviewed the literature up to June 2015 to be discussed at the meeting, and approved the final manuscript. At the time this manuscript was being written, new evidence considered relevant for the debated topics was published, and was consequently included. Several oncological and non-oncological diseases may affect current or future fertility, either caused by the disease itself or the gonadotoxic treatment, and need an adequate FP approach. Women wishing to postpone maternity and transgender individuals before starting hormone therapy or undergoing surgery to remove/alter their reproductive organs should also be counselled accordingly. Embryo and oocyte cryopreservation are first-line FP methods in postpubertal women. Metaphase II oocyte cryopreservation (vitrification) is the preferred option. Cumulative evidence of restoration of ovarian function and spontaneous pregnancies after ART following orthotopic transplantation of cryopreserved ovarian tissue supports its future consideration as an open clinical application. Semen cryopreservation is the only established method for FP in men. Testicular tissue cryopreservation should be recommended in pre-pubertal boys even though fertility restoration strategies by autotransplantation of cryopreserved testicular tissue have not yet been tested for safe clinical use in humans. The establishment of international registries on the short- and long-term outcomes of FP techniques is strongly recommended. Given the lack of studies in large cohorts or with a randomized design, the level of evidence for most of the evidence reviewed was 3 or below. Further high quality studies are needed to study the long-term outcomes of FP techniques. None. N/A.

Down syndrome (trisomy 21) is the most common viable chromosomal disorder with intellectual impairment and several other developmental abnormalities. Here, we report the generation and characterization of induced pluripotent stem cells (iPSCs) derived from monozygotic twins discordant for trisomy 21 in order to eliminate the effects of the variability of genomic background. The alterations observed by genetic analysis at the iPSC level and at first approximation in early development illustrate the developmental disease transcriptional signature of Down syndrome. Moreover, we observed an abnormal neural differentiation of Down syndrome iPSCs in vivo when formed teratoma in NOD‐SCID mice, and in vitro when differentiated into neuroprogenitors and neurons. These defects were associated with changes in the architecture and density of neurons, astroglial and oligodendroglial cells together with misexpression of genes involved in neurogenesis, lineage specification and differentiation. Furthermore, we provide novel evidence that dual‐specificity tyrosine‐( Y )‐phosphorylation regulated kinase 1 A ( DYRK1A ) on chromosome 21 likely contributes to these defects. Importantly, we found that targeting DYRK1A pharmacologically or by shRNA results in a considerable correction of these defects.

STUDY QUESTION: How should surgery for endometriosis be performed? SUMMARY ANSWER: This document provides recommendations covering technical aspects of different methods of surgery for deep endometriosis in women of reproductive age. WHAT IS KNOWN ALREADY: Endometriosis is highly prevalent and often associated with severe symptoms. Yet compared to equally prevalent conditions, it is poorly understood and a challenge to manage. Previously published guidelines have provided recommendations for (surgical) treatment of deep endometriosis, based on the best available evidence, but without technical information and details on how to best perform such treatment in order to be effective and safe. STUDY DESIGN, SIZE, DURATION: A working group of the European Society for Gynaecological Endoscopy (ESGE), ESHRE and the World Endometriosis Society (WES) collaborated on writing recommendations on the practical aspects of surgery for treatment of deep endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: This document focused on surgery for deep endometriosis and is complementary to a previous document in this series focusing on endometrioma surgery. MAIN RESULTS AND THE ROLE OF CHANCE: The document presents general recommendations for surgery for deep endometriosis, starting from preoperative assessments and first steps of surgery. Different approaches for surgical treatment are discussed and are respective of location and extent of disease; uterosacral ligaments and rectovaginal septum with or without involvement of the rectum, urinary tract or extrapelvic endometriosis. In addition, recommendations are provided on the treatment of frozen pelvis and on hysterectomy as a treatment for deep endometriosis. LIMITATIONS, REASONS FOR CAUTION: Owing to the limited evidence available, recommendations are mostly based on clinical expertise. Where available, references of relevant studies were added. WIDER IMPLICATIONS OF THE FINDINGS: These recommendations complement previous guidelines on management of endometriosis and the recommendations for surgical treatment of ovarian endometrioma. STUDY FUNDING/COMPETING INTEREST(S): The meetings of the working group were funded by ESGE, ESHRE and WES. Dr Roman reports personal fees from ETHICON, PLASMASURGICAL, OLYMPUS and NORDIC PHARMA, outside the submitted work; Dr Becker reports grants from Bayer AG, Volition Rx, MDNA Life Sciences and Roche Diagnostics Inc. and other relationships or activities from AbbVie Inc., and Myriad Inc, during the conduct of the study; Dr Tomassetti reports non-financial support from ESHRE, during the conduct of the study; and non-financial support and other were from Lumenis, Gedeon-Richter, Ferring Pharmaceuticals and Merck SA, outside the submitted work. The other authors had nothing to disclose. TRIAL REGISTRATION NUMBER: na